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Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Nov 01; Vol. 22 (21), pp. 6721-7. Date of Electronic Publication: 2012 Sep 05. - Publication Year :
- 2012
-
Abstract
- A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay).<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Azoles chemistry
Azoles pharmacology
Benzoxazoles chemistry
Benzoxazoles pharmacology
Catalytic Domain
Crystallography, X-Ray
Enzyme Activation drug effects
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Ethylamines chemistry
Ethylamines pharmacology
Humans
Inhibitory Concentration 50
Male
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular Structure
Pyridines chemistry
Pyridines pharmacology
Amyloid Precursor Protein Secretases antagonists & inhibitors
Aspartic Acid Endopeptidases antagonists & inhibitors
Azoles chemical synthesis
Benzoxazoles chemical synthesis
Drug Design
Enzyme Inhibitors chemical synthesis
Ethylamines chemical synthesis
Pyridines chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 22
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 23010268
- Full Text :
- https://doi.org/10.1016/j.bmcl.2012.08.097